Table 1.

Alterations of gut microbiota associated with organ fibrosis.

Organ	Gut Microbiome Alterations	Possible Pathways	Mechanisms	Ref
Gut	↑ Gram-negative bacteria (↑LPS) E.g.: Adherent-invasive Escherichia coli; Salmonella Enterica Serovar Typhimurium. ↑ Mucolytic bacteria E.g.: Mucispirillum schaedleri; Ruminococcus; Anaeroplasma; Streptococcus; Lactobacillus.	-Activation of IL-33 mediated pathways; -Activation of Nrf2/Keap1 pathways; -Activation of TLR4/MyD88/NF-κB signalling pathways; -Activation of TNF-L1A (TNF-SF15) pathway.	↑ ECM deposition; ↑ Collagen expression; ↑ Fibroblast migration; ↑ Pro-inflammatory mediators; ↑ Oxidative stress mediators; ↑ Expression of profibrotic mediators (e.g.: TGF-β1, IGF-I, etc.)	[23,24,25,26,27,28,29,30,31,32,33,34,35,36]
Liver	Non-alcoholic liver diseases: ↑ Bacteroidetes ↑ Riminococcus, Bacteriodes vulgatus, Prevotella copri ↑ Alcohol-producing bacteria E.g.: Escherichia coli. ↓ Prevotella Alcoholic liver diseases: ↑ Enterococcaceae, Staphylococcaceae and Enterobacteriaceae ↑ Microorganisms of oral origin E.g.: Veillonella, Streptococcus. ↓ Atopobium ↓ Beneficial autochthonous taxa E.g.: Lachnospiraceae, Ruminococcaceae.	-Activation of hepatic inflammatory immune responses, via portal delivery of PAMPs; -Suppression of Farnesoid-X receptor signalling pathways.	≠ KEGG pathways, namely regarding carbohydrate, lipid and amino acid metabolism; ↑ Intestinal permeability; ↑ Translocation of microbes; ↑ Circulating bacterial endotoxins; ↑ ECM deposition; ↑ Pro-inflammatory mediators; ↑ Generation of reactive oxygen species; ↑Intestinal deconjugation of bile acids; ↑Production of secondary bile acids	[39,40,42,43,44,48,50,51,52]
Kidney	↓ Microbial diversity ↑ Pathogenic species E.g.: Enterobacteriaceae. ↓ Beneficial species E.g.: Bifidobacteriaceae; Lactobacillaceae. ↑ Urease-, urase-, indole-, and para-cresol-producing bacteria ↓Butyrate-producing bacteria	-Activation of TLR4/NF-κB/mitogen-activated protein kinases pathways; -Activation of TGF-β1/Smad pathways; -Activation of renin-angiotensin aldosterone pathway; -Activation of aryl hydrocarbon receptor signalling pathways.	↑ Intestinal permeability; ↑ Circulating bacterial endotoxins; ↑ Uremic toxins (e.g.: TMAO, pCS, IS, IAA); ↓ SCFAs; ↑ Collagen expression; ↑ Pro-inflammatory mediators (e.g.: IL-6, CRP, etc.); ↑ Oxidative stress mediators.	[61,62,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,82,83,84,85,86,87,88,102,103,104,111]
Lung	↑ Bacteroidetes, Lachnospiraceae and Lachnoclostridium ↓ Clostridium spp., Firmicutes, Actinobacteria, Devosia, Clostridiales, Alloprevotella and Rikenellaceae_RC9	-Activation of the TLR4/NF-kB signalling pathway.	↓ SCFAs; ↑ Pro-inflammatory mediators (e.g.: Th17 cells and IL-22).	[124,155,157,159]
Heart	↓ Lactobacillus spp., Bifidobacterium spp., Bacteroides-Prevotella spp.	-Activation of the NLRP3 inflammasome/caspase-1/IL-1β pathway; -Inhibition of cardiac early growth response-1.	↓ Intestinal perfusion; ↑ Collagen expression; ↑ Fibroblast migration; ↓ SCFAs; ↑ Circulating bacterial endotoxins; ↑ Microbial by-products (e.g.: TMAO); ↑ Pro-inflammatory mediators; ↑ Oxidative stress mediators; ≠ Secondary bile acids’ production.	[167,173,175,185,190,194,196]

↑ increased; ↓ decreased; ≠ altered.